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Children constitute 6–10% of all patients attending the emergency department (ED) by emergency medical services (EMS). However, discordant EMS use in children occurs in 37–61% with fever as an important risk factor. We aimed to describe EMS utilisation among febrile children attending European EDs. This study is part of an observational multicentre study assessing management and outcome in febrile children up to 18 years (MOFICHE) attending twelve EDs in eight European countries. Discordant EMS use was defined as the absence of markers of urgency including intermediate/high triage urgency, advanced diagnostics, treatment, and admission in children transferred by EMS. Multivariable logistic regression analyses were performed for the association between (1) EMS use and markers of urgency, and (2) patient characteristics and discordant EMS use after adjusting all analyses for the covariates age, gender, visiting hours, presenting symptoms, and ED setting. A total of 5464 (15%, range 0.1–42%) children attended the ED by EMS. Markers of urgency were more frequently present in the EMS group compared with the non-EMS group. Discordant EMS use occurred in 1601 children (29%, range 1–59%). Age and gender were not associated with discordant EMS use, whereas neurological symptoms were associated with less discordant EMS use (aOR 0.2, 95%CI 0.1–0.2), and attendance out of office hours was associated with more discordant EMS use (aOR 1.6, 95%CI 1.4–1.9). Settings with higher percentage of self-referrals to the ED had more discordant EMS use (p < 0.05). Conclusion: There is large practice variation in EMS use in febrile children attending European EDs. Markers of urgency were more frequently present in children in the EMS group. However, discordant EMS use occurred in 29%. Further research is needed on non-medical factors influencing discordant EMS use in febrile children across Europe, so that pre-emptive strategies can be implemented. What is Known: •Children constitute around 6–10% of all patients attending the emergency department by emergency medical services. •Discordant EMS use occurs in 37–61% of all children, with fever as most common presenting symptom for discordant EMS use in children. What is New: •There is large practice variation in EMS use among febrile children across Europe with discordance EMS use occurring in 29% (range 1–59%), which was associated with attendance during out of office hours and with settings with higher percentage of self-referrals to the ED. •Future research is needed focusing on non-medical factors (socioeconomic status, parental preferences and past experience, healthcare systems, referral pathways, out of hours services provision) that influence discordant EMS use in febrile children across Europe. [ABSTRACT FROM AUTHOR]

Varicella zoster virus episodes in hematological patients were systematically studied retrospectively, and viral persistence for at least 7 days was found in 59% of the episodes. Of the persistent episodes, 50% were complicated and 27% were caused by resistant virus.Background. Varicella zoster virus (VZV) infections are a relevant cause of morbidity and mortality in hematological patients and especially in hematopoietic stem cell transplant (HSCT) recipients. The present study aimed to investigate the prevalence and clinical significance of viral persistence and antiviral resistance by systematically analyzing all episodes of VZV diagnosed in our laboratory in pediatric and adult hematological patients between 2007 and 2010.Methods. Patient charts were reviewed to document patient and disease characteristics. VZV loads were determined in all available clinical samples from the day of diagnosis and thereafter. Persistent VZV infection was defined as a VZV infection that lasted at least 7 days. Analysis of resistance was performed in all patients with persistent VZV infection by sequence analysis of viral thymidine kinase and DNA polymerase genes.Results. In total, 89 episodes occurred in 87 patients, of whom 65 were recipients of an allogeneic HSCT. Follow-up samples were available in 54 episodes. Persistent VZV was demonstrated in 32 of these episodes (59%). Complications occurred in 16 of the persistent episodes (50%) vs 2 of 22 nonpersistent episodes (9%). Mutations possibly associated with resistance were found in 27% of patients with persistent VZV, including patients with treatment-unresponsive dermatomal zoster that progressed to severe retinal or cerebral infection.Conclusions. In hematological patients, VZV-related complications occur frequently, especially in persistent infections. Antiviral resistance is a relevant factor in persistent infections and needs to be investigated in various affected body sites, especially when clinical suspicion of treatment failure arises. [ABSTRACT FROM PUBLISHER]

A correction to the article "Guideline adherence in febrile children below 3 months visiting European Emergency Departments: an observational multicenter study," published online on October 21, 2022 is presented.

Febrile children below 3 months have a higher risk of serious bacterial infections, which often leads to extensive diagnostics and treatment. There is practice variation in management due to differences in guidelines and their usage and adherence. We aimed to assess whether management in febrile children below 3 months attending European Emergency Departments (EDs) was according to the guidelines for fever. This study is part of the MOFICHE study, which is an observational multicenter study including routine data of febrile children (0–18 years) attending twelve EDs in eight European countries. In febrile children below 3 months (excluding bronchiolitis), we analyzed actual management compared to the guidelines for fever. Ten EDs applied the (adapted) NICE guideline, and two EDs applied local guidelines. Management included diagnostic tests, antibiotic treatment, and admission. We included 913 children with a median age of 1.7 months (IQR 1.0–2.3). Management per ED varied as follows: use of diagnostic tests 14–83%, antibiotic treatment 23–54%, admission 34–86%. Adherence to the guideline was 43% (374/868) for blood cultures, 29% (144/491) for lumbar punctures, 55% (270/492) for antibiotic prescriptions, and 67% (573/859) for admission. Full adherence to these four management components occurred in 15% (132/868, range 0–38%), partial adherence occurred in 56% (484/868, range 35–77%). Conclusion: There is large practice variation in management. The guideline adherence was limited, but highest for admission which implies a cautious approach. Future studies should focus on guideline revision including new biomarkers in order to optimize management in young febrile children. What is Known: • Febrile children below 3 months have a higher risk of serious bacterial infections, which often leads to extensive diagnostics and treatment. • There is practice variation in management of young febrile children due to differences in guidelines and their usage and adherence. What is New: • Full guideline adherence is limited, whereas partial guideline adherence is moderate in febrile children below 3 months across Europe. • Guideline revision including new biomarkers is needed to improve management in young febrile children. [ABSTRACT FROM AUTHOR]

Meningococcal disease in the Western countries is frequently caused by Neisseria meningitidis serogroup B. Major efforts have been made to develop a safe and efficacious vaccine against this serogroup which is suitable for use in infants and young children. To assess the quality of the immune response after vaccination with candidate vaccines, laboratory correlates of protection are needed. For serogroups A and C, serum bactericidal activity (SBA) is a well established predictor for protection, but for serogroup B other mechanisms besides SBA may also be involved in conferring protection from disease. Several laboratory methods for identification and evaluation of the immunogenicity of possible vaccine antigens are described in this review. [Copyright &y& Elsevier]

Background Optimization of antimicrobial stewardship is key to tackling antimicrobial resistance, which is exacerbated by overprescription of antibiotics in pediatric emergency departments (EDs). We described patterns of empiric antibiotic use in European EDs and characterized appropriateness and consistency of prescribing. Methods Between August 2016 and December 2019, febrile children attending EDs in 9 European countries with suspected infection were recruited into the PERFORM (Personalised Risk Assessment in Febrile Illness to Optimise Real-Life Management) study. Empiric systemic antibiotic use was determined in view of assigned final "bacterial" or "viral" phenotype. Antibiotics were classified according to the World Health Organization (WHO) AWaRe classification. Results Of 2130 febrile episodes (excluding children with nonbacterial/nonviral phenotypes), 1549 (72.7%) were assigned a bacterial and 581 (27.3%) a viral phenotype. A total of 1318 of 1549 episodes (85.1%) with a bacterial and 269 of 581 (46.3%) with a viral phenotype received empiric systemic antibiotics (in the first 2 days of admission). Of those, the majority (87.8% in the bacterial and 87.0% in the viral group) received parenteral antibiotics. The top 3 antibiotics prescribed were third-generation cephalosporins, penicillins, and penicillin/β-lactamase inhibitor combinations. Of those treated with empiric systemic antibiotics in the viral group, 216 of 269 (80.3%) received ≥1 antibiotic in the "Watch" category. Conclusions Differentiating bacterial from viral etiology in febrile illness on initial ED presentation remains challenging, resulting in a substantial overprescription of antibiotics. A significant proportion of patients with a viral phenotype received systemic antibiotics, predominantly classified as WHO Watch. Rapid and accurate point-of-care tests in the ED differentiating between bacterial and viral etiology could significantly improve antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Objective NR5A1 is a key regulator of sex differentiation and has been implicated in spleen development through transcription activation of TLX1. Concerns exist about hypo- or asplenism in individuals who have a difference of sex development (DSD) due to an NR5A1 disease-causing variant. We aimed to assess spleen anatomy and function in a clinical cohort of such individuals and in their asymptomatic family member carriers. Design Cross-sectional assessment in 22 patients with a DSD or primary ovarian insufficiency and 5 asymptomatic carriers from 18 families, harboring 14 different NR5A1 variants. Methods Spleen anatomy was assessed by ultrasound, spleen function by peripheral blood cell count, white blood cell differentiation, percentage of nonswitched memory B cells, specific pneumococcal antibody response, % pitted red blood cells, and Howell–Jolly bodies. Results Patients and asymptomatic heterozygous individuals had significantly decreased nonswitched memory B cells compared to healthy controls, but higher than asplenic patients. Thrombocytosis and spleen hypoplasia were present in 50% of heterozygous individuals. Four out of 5 individuals homozygous for the previously described p.(Arg103Gln) variant had asplenia. Conclusions Individuals harboring a heterozygous NR5A1 variant that may cause DSD have a considerable risk for functional hyposplenism, irrespective of their gonadal phenotype. Splenic function should be assessed in these individuals, and if affected or unknown, prophylaxis is recommended to prevent invasive encapsulated bacterial infections. The splenic phenotype associated with NR5A1 variants is more severe in homozygous individuals and is, at least for the p.(Arg103Gln) variant, associated with asplenism. [ABSTRACT FROM AUTHOR]

Aim: This study investigated febrile children with petechial rashes who presented to European emergency departments (EDs) and investigated the role that mechanical causes played in diagnoses. Methods: Consecutive patients with fever presenting to EDs in 11 European emergency departments in 2017–2018 were enrolled. The cause and focus of infection were identified and a detailed analysis was performed on children with petechial rashes. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). Results: We found that 453/34010 (1.3%) febrile children had petechial rashes. The focus of the infection included sepsis (10/453, 2.2%) and meningitis (14/453, 3.1%). Children with a petechial rash were more likely than other febrile children to have sepsis or meningitis (OR 8.5, 95% CI 5.3–13.1) and bacterial infections (OR 1.4, 95% CI 1.0–1.8) as well as need for immediate life‐saving interventions (OR 6.6, 95% CI 4.4–9.5) and intensive care unit admissions (OR 6.5, 95% CI 3.0–12.5). Conclusion: The combination of fever and petechial rash is still an important warning sign for childhood sepsis and meningitis. Ruling out coughing and/or vomiting was insufficient to safely identify low‐risk patients. [ABSTRACT FROM AUTHOR]

To assess and describe the aetiology and management of febrile illness in children with primary or acquired immunodeficiency at high risk of serious bacterial infection, as seen in emergency departments in tertiary hospitals. Prospective data on demographics, presenting features, investigations, microbiology, management, and outcome of patients within the 'Biomarker Validation in HR patients' database in PERFORM, were analysed. Immunocompromised children (< 18 years old) presented to fifteen European hospitals in nine countries, and one Gambian hospital, with fever or suspected infection and clinical indication for blood investigations. Febrile episodes were assigned clinical phenotypes using the validated PERFORM algorithm. Logistic regression was used to assess the effect size of predictive features of proven/presumed bacterial or viral infection. A total of 599 episodes in 482 children were analysed. Seventy-eight episodes (13.0%) were definite bacterial, 67 episodes probable bacterial (11.2%), and 29 bacterial syndrome (4.8%). Fifty-five were definite viral (9.2%), 49 probable viral (8.2%), and 23 viral syndrome (3.8%). One hundred ninety were unknown bacterial or viral infections (31.7%), and 108 had inflammatory or other non-infectious causes of fever (18.1%). Predictive features of proven/presumed bacterial infection were ill appearance (OR 3.1 (95% CI 2.1–4.6)) and HIV (OR 10.4 (95% CI 2.0–54.4)). Ill appearance reduced the odds of having a proven/presumed viral infection (OR 0.5 (95% CI 0.3–0.9)). A total of 82.1% had new empirical antibiotics started on admission (N = 492); 94.3% proven/presumed bacterial (N = 164), 66.1% proven/presumed viral (N = 84), and 93.2% unknown bacterial or viral infections (N = 177). Mortality was 1.9% (N = 11) and 87.1% made full recovery (N = 522). Conclusion: The aetiology of febrile illness in immunocompromised children is diverse. In one-third of cases, no cause for the fever will be identified. Justification for standard intravenous antibiotic treatment for every febrile immunocompromised child is debatable, yet effective. Better clinical decision-making tools and new biomarkers are needed for this population. What is Known: • Immunosuppressed children are at high risk for morbidity and mortality of serious bacterial and viral infection, but often present with fever as only clinical symptom. • Current diagnostic measures in this group are not specific to rule out bacterial infection, and positivity rates of microbiological cultures are low. What is New: • Febrile illness and infectious complications remain a significant cause of mortality and morbidity in HR children, yet management is effective. • The aetiology of febrile illness in immunocompromised children is diverse, and development of pathways for early discharge or cessation of intravenous antibiotics is debatable, and requires better clinical decision-making tools and biomarkers. [ABSTRACT FROM AUTHOR]

We aimed to describe characteristics and management of children with comorbidities attending European emergency departments (EDs) with fever. MOFICHE (Management and Outcome of Fever in children in Europe) is a prospective multicentre study (12 European EDs, 8 countries). Febrile children with comorbidities were compared to those without in terms of patient characteristics, markers of disease severity, management, and diagnosis. Comorbidity was defined as a chronic underlying condition that is expected to last > 1 year. We performed multivariable logistic regression analysis, displaying adjusted odds ratios (aOR), adjusting for patient characteristics. We included 38,110 patients, of whom 5906 (16%) had comorbidities. Most common comorbidities were pulmonary, neurologic, or prematurity. Patients with comorbidities more often were ill appearing (20 versus 16%, p < 0.001), had an ED-Paediatric Early Warning Score of > 15 (22 versus 12%, p < 0.001), or a C-reactive protein > 60 mg/l (aOR 1.4 (95%CI 1.3-1.6)). They more often required life-saving interventions (aOR 2.7, 95% CI 2.2-3.3), were treated with intravenous antibiotics (aOR 2.3, 95%CI 2.1-2.5), and were admitted to the ward (aOR 2.2, 95%CI 2.1-2.4) or paediatric intensive care unit (PICU) (aOR 5.5, 95% CI 3.8-7.9). They were more often diagnosed with serious bacterial infections (aOR 1.8, 95%CI 1.7-2.0), including sepsis/meningitis (aOR 4.6, 95%CI 3.2-6.7). Children most at risk for sepsis/meningitis were children with malignancy/immunodeficiency (aOR 14.5, 8.5-24.8), while children with psychomotor delay/neurological disease were most at risk for life-saving interventions (aOR 5.3, 4.1-6.9) or PICU admission (aOR 9.7, 6.1-15.5).Conclusions: Our data show how children with comorbidities are a population at risk, as they more often are diagnosed with bacterial infections and more often require PICU admission and life-saving interventions.What Is Known: • While children with comorbidity constitute a large part of ED frequent flyers, they are often excluded from studies.What Is New: • Children with comorbidities in general are more ill upon presentation than children without comorbidities. • Children with comorbidities form a heterogeneous group; specific subgroups have an increased risk for invasive bacterial infections, while others have an increased risk of invasive interventions such as PICU admission, regardless of the cause of the fever. [ABSTRACT FROM AUTHOR]

Objective: To assess sex differences in presentation and management of febrile children with respiratory symptoms attending European Emergency Departments. Design and setting: An observational study in twelve Emergency Departments in eight European countries. Patients: Previously healthy children aged 0–<18 years with fever (≥ 38°C) at the Emergency Department or in the consecutive three days before Emergency Department visit and respiratory symptoms were included. Main outcome measures: The main outcomes were patient characteristics and management defined as diagnostic tests, treatment and admission. Descriptive statistics were used for patient characteristics and management stratified by sex. Multivariable logistic regression analyses were performed for the association between sex and management with adjustment for age, disease severity and Emergency Department. Additionally, subgroup analyses were performed in children with upper and lower respiratory tract infections and in children below five years. Results: We included 19,781 febrile children with respiratory symptoms. The majority were boys (54%), aged 1–5 years (58%) and triaged as low urgent (67%). Girls presented less frequently with tachypnea (15% vs 16%, p = 0.002) and increased work of breathing (8% vs 12%, p<0.001) compared with boys. Girls received less inhalation medication than boys (aOR 0.82, 95% CI 0.74–0.90), but received antibiotic treatment more frequently than boys (aOR 1.09, 95% CI 1.02–1.15), which is associated with a higher prevalence of urinary tract infections. Amongst children with a lower respiratory tract infection and children below five years girls received less inhalation medication than boys (aOR 0.77, 95% CI 0.66–0.89; aOR 0.80, 95% CI 0.72–0.90). Conclusions: Sex differences concerning presentation and management are present in previously healthy febrile children with respiratory symptoms presenting to the Emergency Department. Future research should focus on whether these differences are related to clinicians' attitudes, differences in clinical symptoms at the time of presentation and disease severity. [ABSTRACT FROM AUTHOR]

Although fatigue is a common symptom in adult patients with primary immunodeficiencies (PID), data in pediatric patients are limited. The goal of this study is to estimate the prevalence and impact of fatigue in children with PID as reported by patients, parents, and health-care providers. A retrospective single-center observational study was performed. Prevalence of fatigue was measured by reviewing medical charts of 54 children in our department who are on immunoglobulin replacement therapy. Both prevalence and impact were also measured by the PedsQL-Multidimensional Fatigue Scale (MFS) in 27 patients and 32 of their parents. This is an age-appropriate questionnaire for self-report of fatigue symptoms in patients aged 5–18 years and for parent proxy reports for patients aged 2–18 years. General, cognitive, and sleep-rest fatigue was measured, and a total fatigue score was calculated. Means, standard deviation and Z scores were calculated using age-specific reference values. Intraclass correlation coefficients (ICC) were calculated for comparison of scores provided by parents vs children's self-reported scores. Both chart review data and PedsQL-MFS showed fatigue rates of 65%. Pediatric PID patients of all ages had significantly lower scores on all subscales and total score of the PedsQL-MFS compared to healthy children, indicating greater perceived symptoms of fatigue. General fatigue was the most affected subscale in PID patients, suggesting that fatigue in these patients is mainly physical. Seventy-four percent of PID patients had a Z score lower than − 1 on the general fatigue subscale indicating severe fatigue. Child-parent concordance varied between 0.24 and 0.93. Our results show the feasibility of the PedsQL-MFS survey to evaluate the prevalence and severity of fatigue in children with PID and underscore the importance of this issue in our patient care. [ABSTRACT FROM AUTHOR]

Proximal duplications of chromosome 1q are rare chromosomal abnormalities. Most patients with this condition present with neurological, urogenital, and congenital heart disease and short life expectancy. Mosaicism for trisomy 1q10q23.3 has only been reported once in the literature. Here we discuss a second case: a girl with a postnatal diagnosis of a de novo pure mosaic trisomy 1q1023.3 who has no urogenital or cardiac anomalies. [ABSTRACT FROM AUTHOR]

An impaired immune response could play a role in the acquisition of secondary infections in critically ill children. Human leukocyte antigen-DR expression on monocytes (mHLA-DR) has been proposed as marker to detect immunosuppression, but its potential to predict secondary infections in critically ill children is unclear. We aimed to assess the association between mHLA-DR expression at several timepoints and the change of mHLA-DR expression over time with the acquisition of secondary infections in critically ill children. In this prospective observational study, children < 18 years with fever and/or suspected infection (community-acquired or hospital-acquired) were included at a paediatric intensive care unit in the Netherlands. mHLA-DR expression was determined by flow cytometry on day 1, day 2–3 and day 4–7. The association between delta-mHLA-DR expression (difference between last and first measurement) and secondary infection was assessed by multivariable regression analysis, adjusted for age and Paediatric Logistic Organ Dysfunction-2 score. We included 104 patients at the PICU (median age 1.2 years [IQR 0.3–4.2]), of whom 28 patients (27%) developed a secondary infection. Compared to 93 healthy controls, mHLA-DR expression of critically ill children was significantly lower at all timepoints. mHLA-DR expression did not differ at any of the time points between patients with and without secondary infection. In addition, delta-mHLA-DR expression was not associated with secondary infection (aOR 1.00 [95% CI 0.96–1.04]). Conclusions: Our results confirm that infectious critically ill children have significantly lower mHLA-DR expression than controls. mHLA-DR expression was not associated with the acquisition of secondary infections. What is Known: • An impaired immune response, estimated by mHLA-DR expression, could play an essential role in the acquisition of secondary infections in critically ill children. • In critically ill children, large studies on the association of mHLA-DR expression with secondary infections are scarce. What is New: • Our study confirms that critically ill children have lower mHLA-DR expression than healthy controls. • mHLA-DR expression and change in mHLA-DR was not associated with the acquisition of secondary infection. [ABSTRACT FROM AUTHOR]

Objectives: Hospitalisation is frequently used as a marker of disease severity in observational Emergency Department (ED) studies. The comparison of ED admission rates is complex in potentially being influenced by the characteristics of the region, ED, physician and patient. We aimed to study variation in ED admission rates of febrile children, to assess whether variation could be explained by disease severity and to identify patient groups with large variation, in order to use this to reduce unnecessary health care utilization that is often due to practice variation. Design: MOFICHE (Management and Outcome of Fever in children in Europe, part of the PERFORM study, www.perform2020.org), is a prospective cohort study using routinely collected data on febrile children regarding patient characteristics (age, referral, vital signs and clinical alarming signs), diagnostic tests, therapy, diagnosis and hospital admission. Setting and participants: Data were collected on febrile children aged 0–18 years presenting to 12 European EDs (2017–2018). Main outcome measures: We compared admission rates between EDs by using standardised admission rates after adjusting for patient characteristics and initiated tests at the ED, where standardised rates >1 demonstrate higher admission rates than expected and rates <1 indicate lower rates than expected based on the ED patient population. Results: We included 38,120 children. Of those, 9.695 (25.4%) were admitted to a general ward (range EDs 5.1–54.5%). Adjusted standardised admission rates ranged between 0.6 and 1.5. The largest variation was seen in short admission rates (0.1–5.0), PICU admission rates (0.2–2.2), upper respiratory tract infections (0.4–1.7) and fever without focus (0.5–2.7). Variation was small in sepsis/meningitis (0.9–1.1). Conclusions: Large variation exists in admission rates of febrile children evaluated at European EDs, however, this variation is largely reduced after correcting for patient characteristics and therefore overall admission rates seem to adequately reflect disease severity or a potential for a severe disease course. However, for certain patient groups variation remains high even after adjusting for patient characteristics. [ABSTRACT FROM AUTHOR]

Purpose: While neonatal bloodspot screening (NBS) for severe combined immunodeficiency (SCID) has been introduced more than a decade ago, implementation in NBS programs remains challenging in many countries. Even if high-quality test methods and follow-up care are available, public uptake and parental acceptance are not guaranteed. The aim of this study was to describe the parental perspective on NBS for SCID in the context of an implementation pilot. Psychosocial aspects have never been studied before for NBS for SCID and are important for societal acceptance, a major criterion when introducing new disorders in NBS programs. Methods: To evaluate the perspective of parents, interviews were conducted with parents of newborns with abnormal SCID screening results (N = 17). In addition, questionnaires about NBS for SCID were sent to 2000 parents of healthy newborns who either participated or declined participation in the SONNET-study that screened 140,593 newborns for SCID. Results: Support for NBS for SCID was expressed by the majority of parents in questionnaires from both a public health perspective and a personal perspective. Parents emphasized the emotional impact of an abnormal screening result in interviews. (Long-term) stress and anxiety can be experienced during and after referral indicating the importance of uniform follow-up protocols and adequate information provision. Conclusion: The perspective of parents has led to several recommendations for NBS programs that are considering screening for SCID or other disorders. A close partnership of NBS programs' stakeholders, immunologists, geneticists, and pediatricians-immunologists in different countries is required for moving towards universal SCID screening for all infants. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Febrile illness in high‑risk children: a prospective, international observational study."

Case Presentation: A 3-year-old girl was referred to a pediatric pulmonologist for dyspnea and recurrent upper respiratory tract infections (RTIs). The patient was born full term to unrelated Dutch parents after an uneventful pregnancy and birth. The year before presentation, she had suffered from pneumonia and > 10 upper RTIs. Apart from the recurrent RTIs, which started in infancy, her medical history was not significant and did not include allergies or eczema. An adenotonsillectomy was performed at the age of 2 years, and she was treated with multiple antibiotic regimens and inhalation therapy with salbutamol and corticosteroids, with no relief of symptoms. [ABSTRACT FROM AUTHOR]

In June and July 2016, we identified 8 adults and 17 children with respiratory enterovirus D68 infections. Thirteen children required intensive care unit admission because of respiratory insufficiency, and 1 had concomitant acute flaccid myelitis. Phylogenetic analysis showed that all of 20 sequences obtained belong to the recently described clade B3. [ABSTRACT FROM AUTHOR]

Cidofovir is frequently used to treat life-threatening human adenovirus (HAdV) infections in immunocompromised children after hematopoietic stem cell transplantation (HSCT). However, the antiviral effect irrespective of T cell reconstitution remains unresolved. Plasma HAdV DNA levels were monitored by real-time quantitative PCR during 42 cidofovir treatment episodes for HAdV viremia in 36 pediatric allogeneic HSCT recipients. HAdV load dynamics were related to T and natural killer (NK) cell reconstitution measured by flow cytometry. To evaluate the in vivo antiadenoviral effect of cidofovir, we focused on 20 cidofovir treatment episodes lacking concurrent T cell reconstitution. During 2 to 10 weeks of follow-up in the absence of T cells, HAdV load reduction (n = 7) or stabilization (n = 8) was observed in 15 of 20 treatments. Although HAdV load reduction was always accompanied by NK cell expansion, HAdV load stabilization was measured in 2 children lacking both T and NK cell reconstitution. In cases with T cell reconstitution, rapid HAdV load reduction (n = 14) or stabilization (n = 6) was observed in 20 of 22 treatments. In the absence of T cells, cidofovir treatment was associated with HAdV viremia control in the majority of cases. Although the contribution of NK cells cannot be excluded, cidofovir has the potential to mediate HAdV load stabilization in the time pending T cell reconstitution. [ABSTRACT FROM AUTHOR]

Background: In chronic granulomatous disease allogeneic haemopoietic stem-cell transplantation (HSCT) in adolescents and young adults and patients with high-risk disease is complicated by graft-failure, graft-versus-host disease (GVHD), and transplant-related mortality. We examined the effect of a reduced-intensity conditioning regimen designed to enhance myeloid engraftment and reduce organ toxicity in these patients. Methods: This prospective study was done at 16 centres in ten countries worldwide. Patients aged 0-40 years with chronic granulomatous disease were assessed and enrolled at the discretion of individual centres. Reduced-intensity conditioning consisted of high-dose fludarabine (30 mg/m2 [infants <9 kg 1-2 mg/kg]; one dose per day on days -8 to -3), serotherapy (anti-thymocyte globulin [10 mg/kg, one dose per day on days -4 to -1; or thymoglobuline 2-5 mg/kg, one dose per day on days -5 to -3]; or low-dose alemtuzumab [<1 mg/kg on days -8 to -6]), and low-dose (50-72% of myeloablative dose) or targeted busulfan administration (recommended cumulative area under the curve: 45-65 mg/Lxh). Busulfan was administered mainly intravenously and exceptionally orally from days -5 to -3. Intravenous busulfan was dosed according to weight-based recommendations and was administered in most centres (ten) twice daily over 4 h. Unmanipulated bone marrow or peripheral blood stem cells from HLA-matched related- donors or HLA-9/10 or HLA-10/10 matched unrelated-donors were infused. The primary endpoints were overall survival and event-free survival (EFS), probabilities of overall survival and EFS at 2 years, incidence of acute and chronic GVHD, achievement of at least 90% myeloid donor chimerism, and incidence of graft failure after at least 6 months of follow-up. Findings 56 patients (median age 12-7 years; IQR 6-8-17-3) with chronic granulomatous disease were enrolled from June 15, 2003, to Dec 15, 2012. 42 patients (75%) had high-risk features (ie, intractable infections and autoinflammation), 25 (45%) were adolescents and young adults (age 14-39 years). 21 HLA-matched related-donor and 35 HLA-matched unrelated-donor transplants were done. Median time to engraftment was 19 days (IQR 16-22) for neutrophils and 21 days (IQR 16-25) for platelets. At median follow-up of 21 months (IQR 13-35) overall survival was 93% (52 of 56) and EFS was 89% (50 of 56). The 2-year probability of overall survival was 96% (95% CI 86-46-99-09) and of EFS was 91% (79-78-96-17). Graft-failure occurred in 5% (three of 56) of patients. The cumulative incidence of acute GVHD of grade III-IV was 4% (two of 56) and of chronic graft-versus-host disease was 7% (four of 56). Stable (>90%) myeloid donor chimerism was documented in 52 (93%) surviving patients. Interpretation: This reduced-intensity conditioning regimen is safe and efficacious in high-risk patients with chronic granulomatous disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of cholesterol and lipoproteins in children with severe meningococcal sepsis.Design: Retrospective observational study.Setting: A university-affiliated pediatric intensive care unit.Patients: Fifty-seven patients admitted to the pediatric intensive care unit with meningococcal sepsis or septic shock.Interventions: Total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) concentrations were measured in serum samples drawn within 6 hrs after admission to the pediatric intensive care unit and 12, 24, 48, 72 hrs, 7 days, and 1-3 months afterward. Standard deviation scores of these variables (sd scores) were calculated to correct for age-related differences. To assess disease severity, the Pediatric Risk of Mortality (PRISM) score, the Sepsis-related Organ Failure Assessment (SOFA) score, and the Disseminated Intravascular Coagulation (DIC) score were determined as well as selected laboratory variables.Measurements and Main Results: Ten patients died. Total serum cholesterol on admission was very low in all patients. This hypocholesterolemia was caused by low HDL concentrations but in particular by low LDL cholesterol levels. Eight patients had undetectable LDL levels on admission. Total cholesterol levels were significantly lower in nonsurvivors than in survivors (0.97 vs. 1.60, p = .013), whereas levels of LDL and HDL did not significantly differ between both groups. Total cholesterol sd scores were similar between survivors and nonsurvivors. Within survivors, cholesterol sd score was significantly lower in patients with shock compared with those with sepsis. The total cholesterol, HDL, and LDL levels correlated with clinical variables of disease severity and with levels of cytokines. Total cholesterol, HDL, and LDL levels normalized rapidly in survivors and were completely normal 1-3 months after admission.Conclusions: Extremely low levels of total serum cholesterol, HDL, and LDL are found in the initial phase of children with severe meningococcal disease. Total cholesterol levels are significantly lower in nonsurvivors than in survivors, but not the sd score. Total cholesterol, HDL, and LDL levels on admission are inversely associated with disease severity. Hypocholesterolism is associated with hypocortisolism. The concentrations of total cholesterol and lipoproteins steadily increase after 24 hrs in survivors and are normalized 1-3 months after pediatric intensive care unit admission. [ABSTRACT FROM AUTHOR]